Methods and Compositions for Articular Repair

ABSTRACT

Disclosed herein are methods and compositions for producing articular repair materials and for repairing an articular surface. In particular, methods for providing articular repair systems. Also provided are articular surface repair systems designed to replace a selected area cartilage, for example, and surgical tools for repairing articular surfaces.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. Ser. No. 12/777,859 entitled“METHODS AND COMPOSITIONS FOR ARTICULAR REPAIR,” filed May 11, 2010,which in turn is a continuation of U.S. Ser. No. 12/317,472 entitled“METHODS AND COMPOSITIONS FOR ARTICULAR REPAIR,” filed Dec. 22, 2008,which in turn is a continuation of U.S. Ser. No. 10/305,652, entitled“METHODS AND COMPOSITIONS FOR ARTICULAR REPAIR,” filed Nov. 27, 2002,which in turn is a continuation-in-part of U.S. Ser. No. 10/160,667entitled “METHODS AND COMPOSITIONS FOR ARTICULAR RESURFACING,” filed May28, 2002, which in turn claims the benefit of U.S. Ser. No. 60/293,488entitled “METHODS TO IMPROVE CARTILAGE REPAIR SYSTEMS,” filed May 25,2001, U.S. Ser. No. 60/363,527, entitled “NOVEL DEVICES FOR CARTILAGEREPAIR,” filed Mar. 12, 2002 and U.S. Ser. Nos. 60/380,695 and60/380,692, entitled “METHODS AND COMPOSITIONS FOR CARTILAGE REPAIR,”and “METHODS FOR JOINT REPAIR,” filed May 14, 2002, all of whichapplications are hereby incorporated by reference in their entireties.

TECHNICAL FIELD

The present invention relates to orthopedic methods, systems andprosthetic devices and more particularly relates to methods, systems anddevices for articular resurfacing.

BACKGROUND

There are various types of cartilage, e.g., hyaline cartilage andfibrocartilage. Hyaline cartilage is found at the articular surfaces ofbones, e.g., in the joints, and is responsible for providing the smoothgliding motion characteristic of moveable joints. Articular cartilage isfirmly attached to the underlying bones and measures typically less than5 mm in thickness in human joints, with considerable variation dependingon joint and site within the joint. In addition, articular cartilage isaneural, avascular, and alymphatic. In adult humans, this cartilagederives its nutrition by a double diffusion system through the synovialmembrane and through the dense matrix of the cartilage to reach thechondrocyte, the cells that are found in the connective tissue ofcartilage.

Adult cartilage has a limited ability of repair; thus, damage tocartilage produced by disease, such as rheumatoid and/or osteoarthritis,or trauma can lead to serious physical deformity and debilitation.Furthermore, as human articular cartilage ages, its tensile propertieschange. The superficial zone of the knee articular cartilage exhibits anincrease in tensile strength up to the third decade of life, after whichit decreases markedly with age as detectable damage to type II collagenoccurs at the articular surface. The deep zone cartilage also exhibits aprogressive decrease in tensile strength with increasing age, althoughcollagen content does not appear to decrease. These observationsindicate that there are changes in mechanical and, hence, structuralorganization of cartilage with aging that, if sufficiently developed,can predispose cartilage to traumatic damage.

Usually, severe damage or loss of cartilage is treated by replacement ofthe joint with a prosthetic material, for example, silicone, e.g. forcosmetic repairs, or metal alloys. See, e.g., U.S. Pat. No. 6,383,228,issued May 7, 2002; U.S. Pat. No. 6,203,576, issued Mar. 20, 2001; U.S.Pat. No. 6,126,690, issued Oct. 3, 2000. Implantation of theseprosthetic devices is usually associated with loss of underlying tissueand bone without recovery of the full function allowed by the originalcartilage and, with some devices, serious long-term complicationsassociated with the loss of significant amount of tissue and bone caninclude infection, osteolysis and also loosening of the implant.

Further, joint arthroplasties are highly invasive and require surgicalresection of the entire or the majority of the articular surface of oneor more bones. With these procedures, the marrow space is reamed inorder to fit the stem of the prosthesis. The reaming results in a lossof the patient's bone stock.

Osteolysis will frequently lead to loosening of the prosthesis. Theprosthesis will subsequently have to be replaced. Since the patient'sbone stock is limited, the number of possible replacement surgeries isalso limited for joint arthroplasty. In short, over the course of 15 to20 years, and in some cases shorter time periods, the patients may runout of therapeutic options resulting in a very painful, non-functionaljoint.

The use of matrices, tissue scaffolds or other carriers implanted withcells (e.g., chrondrocytes, chondrocyte progenitors, stromal cells,mesenchymal stem cells, etc.) has also been described as a potentialtreatment for cartilage repair. See, also, International PublicationsWO; 99/51719; WO 01/91672 and WO 01/17463; U.S. Pat. No. 5,283,980 B1,issued Sep. 4, 2001; U.S. Pat. No. 5,842,477, issued Dec. 1, 1998; U.S.Pat. No. 5,769,899, issued Jun. 23, 1998; U.S. Pat. No. 4,609,551,issued Sep. 2, 1986; U.S. Pat. No. 5,041,138, issued Aug. 20, 199; U.S.Pat. No. 5,197,985, issued Mar. 30, 1993; U.S. Pat. No. 5,226,914,issued Jul. 13, 1993; U.S. Pat. No. 6,328,765, issued Dec. 11, 2001;U.S. Pat. No. 6,281,195, issued Aug. 28, 2001; and U.S. Pat. No.4,846,835, issued Jul. 11, 1989. However, clinical outcomes withbiologic replacement materials such as allograft and autograft systemsand tissue scaffolds have been uncertain since most of these materialscannot achieve a morphologic arrangement or structure similar to oridentical to that of normal, disease-free human tissue. Moreover, themechanical durability of these biologic replacement materials is notcertain.

Despite the large number of studies in the area of cartilage repair, theintegration of the cartilage replacement material with the surroundingcartilage of the patient has proven difficult. In particular,integration can be extremely difficult due to differences in thicknessand curvature between the surrounding cartilage and/or the underlyingsubchondral bone and the cartilage replacement material.

Thus, there remains a need for methods and compositions for jointrepair, including methods and compositions that facilitate theintegration between the cartilage replacement system and the surroundingcartilage.

SUMMARY

The present invention provides novel devices and methods for replacing aportion (e.g., diseased area and/or area slightly larger than thediseased area) of a joint (e.g., cartilage and/or bone) with anon-pliable, non-liquid (e.g., hard) implant material, where theimplant—achieves a near anatomic fit with the surrounding structures andtissues. In cases where the devices and/or methods include an elementassociated with the underlying articular bone, the invention alsoprovides that the bone-associated element achieves a near anatomicalignment with the subchondral bone. The invention also provides for thepreparation of an implantation site with a single cut.

In one aspect, the invention includes a method for providing articularreplacement material, the method comprising the step of producingarticular replacement (e.g., cartilage replacement material) of selecteddimensions (e.g., size, thickness and/or curvature).

In another aspect, the invention includes a method of making cartilagerepair material, the method comprising the steps of (a) measuring thedimensions (e.g., thickness, curvature and/or size) of the intendedimplantation site or the dimensions of the area surrounding the intendedimplantation site; and (b) providing cartilage replacement material thatconforms to the measurements obtained in step (a). In certain aspects,step (a) comprises measuring the thickness of the cartilage surroundingthe intended implantation site and measuring the curvature of thecartilage surrounding the intended implantation site. In otherembodiments, step (a) comprises measuring the size of the intendedimplantation site and measuring the curvature of the cartilagesurrounding the intended implantation site. In other embodiments, step(a) comprises measuring the thickness of the cartilage surrounding theintended implantation site, measuring the size of the intendedimplantation site, and measuring the curvature of the cartilagesurrounding the intended implantation site. In other embodiments, step(a) comprises reconstructing the shape of healthy cartilage surface atthe intended implantation site.

In any of the methods described herein, one or more components of thearticular replacement material (e.g., the cartilage replacementmaterial) are non-pliable, non-liquid, solid or hard. The dimensions ofthe replacement material may be selected following intraoperativemeasurements, for example measurements made using imaging techniquessuch as ultrasound, MRI, CT scan, x-ray imaging obtained with x-ray dyeand fluoroscopic imaging. A mechanical probe (with or without imagingcapabilities) may also be used to selected dimensions, for example anultrasound probe, a laser, an optical probe and a deformable material.

In any of the methods described herein, the replacement material may beselected (for example, from a pre-existing library of repair systems),grown from cells and/or hardened from various materials. Thus, thematerial can be produced pre- or post-operatively. Furthermore, in anyof the methods described herein the repair material may also be shaped(e.g., manually, automatically or by machine), for example usingmechanical abrasion, laser ablation, radiofrequency ablation,cryoablation and/or enzymatic digestion.

In any of the methods described herein, the articular replacementmaterial may comprise synthetic materials (e.g., metals, polymers,alloys or combinations thereof) or biological materials such as stemcells, fetal cells or chondrocyte cells.

In another aspect, the invention includes a method of repairing acartilage in a subject, the method of comprising the step of implantingcartilage repair material prepared according to any of the methodsdescribed herein.

In yet another aspect, the invention provides a method of determiningthe curvature of an articular surface, the method comprising the step ofintraoperatively measuring the curvature of the articular surface usinga mechanical probe. The articular surface may comprise cartilage and/orsubchondral bone. The mechanical probe (with or without imagingcapabilities) may include, for example an ultrasound probe, a laser, anoptical probe and/or a deformable material.

In a still further aspect, the invention provides a method of producingan articular replacement material comprising the step of providing anarticular replacement material that conforms to the measurementsobtained by any of the methods of described herein.

In a still further aspect, the invention includes a partial or fullarticular prosthesis comprising a first component comprising a cartilagereplacement material; and a second component comprising one or moremetals, wherein said second component has a curvature similar tosubchondral bone, wherein said prosthesis comprises less than about 80%of the articular surface. In certain embodiments, the first and/orsecond component comprises a non-pliable material (e.g., a metal, apolymer, a metal allow, a solid biological material). Other materialsthat may be included in the first and/or second components includepolymers, biological materials, metals, metal alloys or combinationsthereof. Furthermore, one or both components may be smooth or porous (orporous coated). In certain embodiments, the first component exhibitsbiomechanical properties (e.g., elasticity, resistance to axial loadingor shear forces) similar to articular cartilage. The first and/or secondcomponent can be bioresorbable and, in addition, the first or secondcomponents may be adapted to receive injections.

In another aspect, an articular prosthesis comprising an externalsurface located in the load bearing area of an articular surface,wherein the dimensions of said external surface achieve a near anatomicfit with the adjacent cartilage is provided. The prosthesis of maycomprise one or more metals or metal alloys.

In yet another aspect, an articular repair system comprising (a)cartilage replacement material, wherein said cartilage replacementmaterial has a curvature similar to surrounding or adjacent cartilage;and (b) at least one non-biologic material, wherein said articularsurface repair system comprises a portion of the articular surface equalto, smaller than, or greater than, the weight-bearing surface isprovided. In certain embodiments, the cartilage replacement material isnon-pliable (e.g., hard hydroxyapatite, etc.). In certain embodiments,the system exhibits biomechanical (e.g., elasticity, resistance to axialloading or shear forces) and/or biochemical properties similar toarticular cartilage. The first and/or second component can bebioresorbable and, in addition, the first or second components may beadapted to receive injections.

In a still further aspect of the invention, an articular surface repairsystem comprising a first component comprising a cartilage replacementmaterial, wherein said first component has dimensions similar to that ofadjacent or surrounding cartilage; and a second component, wherein saidsecond component has a curvature similar to subchondral bone, whereinsaid articular surface repair system comprises less than about 80% ofthe articular surface (e.g., a single femoral condyle, tibia, etc.) isprovided. In certain embodiments, the first component is non-pliable(e.g., hard hydroxyapatite, etc.). In certain embodiments, the systemexhibits biomechanical (e.g., elasticity, resistance to axial loading orshear forces) and/or biochemical properties similar to articularcartilage. The first and/or second component can be bioresorbable and,in addition, the first or second components may be adapted to receiveinjections. In certain embodiments, the first component has a curvatureand thickness similar to that of adjacent or surrounding cartilage. Thethickness and/or curvature may vary across the implant material.

In a still further embodiment, a partial articular prosthesis comprising(a) a metal or metal alloy; and (b) an external surface located in theload bearing area of an articular surface, wherein the external surfacedesigned to achieve a near anatomic fit with the adjacent cartilage isprovided.

Any of the repair systems or prostheses described herein (e.g., theexternal surface) may comprise a polymeric material, for exampleattached to said metal or metal alloy. Further, any of the systems orprostheses described herein can be adapted to receive injections, forexample, through an opening in the external surface of said cartilagereplacement material (e.g., an opening in the external surfaceterminates in a plurality of openings on the bone surface). Bone cement,therapeutics, and/or other bioactive substances may be injected throughthe opening(s). In certain embodiments, bone cement is injected underpressure in order to achieve permeation of portions of the marrow spacewith bone cement. In addition, any of the repair systems or prosthesesdescribed herein may be anchored in bone marrow or in the subchondralbone itself. One or more anchoring extensions (e.g., pegs, etc.) mayextend through the bone and/or bone marrow.

In any of the embodiments and aspects described herein, the joint can bea knee, shoulder, hip, vertebrae, elbow, ankle, etc.

In another aspect, a method of designing an articular implant comprisingthe steps of obtaining an image of a joint, wherein the image includesboth normal cartilage and diseased cartilage; reconstructing dimensionsof the diseased cartilage surface to correspond to normal cartilage; anddesigning the articular implant to match the dimensions of thereconstructed diseased cartilage surface or to match an area slightlygreater than the diseased cartilage surface is provided. The image canbe, for example, MRI, CT, ultrasound, digital tomosynthesis and/oroptical coherence tomography images. In certain embodiments,reconstruction is performed by obtaining a parametric surface thatfollows the contour of the normal cartilage. The parametric surface caninclude control points that extend the contour of the normal cartilageto the diseased cartilage and/or a B-spline surface. In otherembodiments, the reconstruction is performed by obtaining a binary imageof cartilage by extracting cartilage from the image, wherein diseasedcartilage appears as indentations in the binary image; and performing amorphological closing operation (e.g., performed in two orthree-dimensions using a structuring element and/or a dilation operationfollowed by an erosion operation) to determine the shape of an implantto fill the areas of diseased cartilage.

In yet another aspect, described herein are systems for evaluating thefit of an articular repair system into a joint, the systems comprisingone or more computing means capable of superimposing a three-dimensional(e.g., three-dimensional representations of at least one articularstructure and of the articular repair system) or a two-dimensionalcross-sectional image (e.g., cross-sectional images reconstructed inmultiple planes) of a joint and an image of an articular repair systemto determine the fit of the articular repair system. The computing meansmay be: capable of merging the images of the joint and the articularrepair system into common coordinate system; capable of selecting anarticular repair system having the best fit; capable of rotating ormoving the images with respect to each other; and/or capablehighlighting areas of poor alignment between the articular repair systemand the surrounding articular surfaces. The three-dimensionalrepresentations may be generated using a parametric surfacerepresentation.

In yet another aspect, surgical tool for preparing a joint to receive animplant are described, for example a tool comprising one or moresurfaces or members that conform to the shape of the articular surfacesof the joint (e.g., a femoral condyle and/or tibial plateau of a kneejoint). In certain embodiments, the tool comprises lucite and/orsilastic. The tool can be re-useable or single-use. In certainembodiments, the tool comprises an array of adjustable, closely spacedpins. In any embodiments described herein, the surgical tool may furthercomprising an aperture therein, for example one or more apertures havingdimensions (e.g., diameter, depth, etc.) smaller or equal to one or moredimensions of the implant and/or one or more apertures adapted toreceive one or more injectables. Any of the tools described herein mayfurther include one or more curable (hardening) materials orcompositions, for example that are injected through one or moreapertures in the tool and which solidify to form an impression of thearticular surface.

In still another aspect, method of evaluating the fit of an articularrepair system into a joint is described herein, the method comprisingobtaining one or more three-dimensional images (e.g., three-dimensionalrepresentations of at least one articular structure and of the articularrepair system) or two-dimensional cross-sectional images (e.g.,cross-sectional images reconstructed in multiple planes) of a joint,wherein the joint includes at least one defect or diseased area;obtaining one or more images of one or more articular repair systemsdesigned to repair the defect or diseased area; and evaluating theimages to determine the articular repair system that best fits thedefect (e.g., by superimposing the images to determine the fit of thearticular repair system into the joint). In certain embodiments, theimages of the joint and the articular repair system are merged intocommon coordinate system. The three-dimensional representations may begenerated using a parametric surface representation. In any of thesemethods, the evaluation may be performed by manual visual inspectionand/or by computer (e.g., automated). The images may be obtained, forexample, using a C-arm system and/or radiographic contrast.

In yet another aspect, described herein is a method of placing animplant into an articular surface having a defect or diseased area, themethod comprising the step of imaging the joint using a C-arm systemduring placement of the implant, thereby accurately placing the implantinto a defect or diseased area.

These and other embodiments of the subject invention will readily occurto those of skill in the art in light of the disclosure herein.

BRIEF DESCRIPTION OF THE FIGURES

The foregoing features of the invention will be more readily understoodby reference to the following detailed description, taken with referenceto the accompanying drawings, in which:

FIG. 1 is a flowchart depicting various methods of the present inventionincluding, measuring the size of an area of diseased cartilage orcartilage loss, measuring the thickness of the adjacent cartilage, andmeasuring the curvature of the articular surface and/or subchondralbone. Based on this information, a best fitting implant can be selectedfrom a library of implants or a patient specific custom implant can begenerated. The implantation site is subsequently prepared and theimplantation is performed.

FIG. 2 is a reproduction of a three-dimensional thickness map of thearticular cartilage of the distal femur. Three-dimensional thicknessmaps can be generated, for example, from ultrasound, CT or MRI data.Dark holes within the substances of the cartilage indicate areas of fullthickness cartilage loss.

FIG. 3 shows an example of a Placido disc of concentrically arrangedcircles of light.

FIG. 4 shows an example of a projected Placido disc on a surface offixed curvature.

FIG. 5 shows an example of a 2D topographical map of an irregularlycurved surface.

FIG. 6 shows an example of a 3D topographical map of an irregularlycurved surface.

FIG. 7 shows a reflection resulting from a projection of concentriccircles of light (Placido Disk) on each femoral condyle, demonstratingthe effect of variation in surface contour on the reflected circles.

FIG. 8A-H are schematics of various stages of knee resurfacing. FIG. 8Ashows an example of normal thickness cartilage in the anterior, centraland posterior portion of a femoral condyle 800 and a cartilage defect805 in the posterior portion of the femoral condyle. FIG. 8B shows animaging technique or a mechanical, optical, laser or ultrasound devicemeasuring the thickness and detecting a sudden change in thicknessindicating the margins of a cartilage defect 810. FIG. 8C shows aweight-bearing surface 815 mapped onto the articular cartilage.Cartilage defect 805 is located within the weight-bearing surface 815.FIG. 8D shows an intended implantation site (stippled line) 820 andcartilage defect 805. The implantation site 820 is slightly larger thanthe area of diseased cartilage 805. FIG. 8E depicts placement of anexemplary single component articular surface repair system 825. Theexternal surface of the articular surface repair system 826 has acurvature similar to that of the surrounding cartilage 800 resulting ingood postoperative alignment between the surrounding normal cartilage800 and the articular surface repair system 825. FIG. 8F shows anexemplary multi-component articular surface repair system 830. Thedistal surface of the deep component 832 has a curvature similar to thatof the adjacent subchondral bone 835. The external surface of thesuperficial component 837 has a thickness and curvature similar to thatof the surrounding normal cartilage 800. FIG. 8G shows an exemplarysingle component articular surface repair system 840 with a peripheralmargin 845 substantially non-perpendicular to the surrounding oradjacent normal cartilage 800. FIG. 8H shows an exemplarymulti-component articular surface repair system 850 with a peripheralmargin 845 substantially non-perpendicular to the surrounding oradjacent normal cartilage 800.

FIG. 9, A through E, are schematics depicting exemplary knee imaging andresurfacing. FIG. 9A is a schematic depicting a magnified view of anarea of diseased cartilage 905 demonstrating decreased cartilagethickness when compared to the surrounding normal cartilage 900. Themargins 910 of the defect have been determined. FIG. 9B is a schematicdepicting measurement of cartilage thickness 915 adjacent to the defect905. FIG. 9C is a schematic depicting placement of a multi-componentmini-prosthesis 915 for articular resurfacing. The thickness 920 of thesuperficial component 923 closely approximates that of the adjacentnormal cartilage 900 and varies in different regions of the prosthesis.The curvature of the distal portion of the deep component 925 is similarto that of the adjacent subchondral bone 930. FIG. 9D is a schematicdepicting placement of a single component mini-prosthesis 940 utilizingfixturing stems 945. FIG. 9E depicts placement of a single componentmini-prosthesis 940 utilizing fixturing stems 945 and an opening 950 forinjection of bone cement 955. The mini-prosthesis has an opening at theexternal surface 950 for injecting bone cement 955 or other liquids. Thebone cement 955 can freely extravasate into the adjacent bone and marrowspace from several openings at the undersurface of the mini-prosthesis960 thereby anchoring the mini-prosthesis.

FIG. 10A to C, are schematics depicting other exemplary knee resurfacingdevices and methods. FIG. 10A is a schematic depicting normal thicknesscartilage in the anterior and central and posterior portion of a femoralcondyle 1000 and a large area of diseased cartilage 1005 in theposterior portion of the femoral condyle. FIG. 10B depicts placement ofa single component articular surface repair system 1010. Theimplantation site has been prepared with a single cut. The articularsurface repair system is not perpendicular to the adjacent normalcartilage 1000. FIG. 10C depicts a multi-component articular surfacerepair system 1020. The implantation site has been prepared with asingle cut. The deep component 1030 has a curvature similar to that ofthe adjacent subchondral bone 1035. The superficial component 1040 has acurvature similar to that of the adjacent cartilage 1000.

FIGS. 11A and B show exemplary single and multiple component devices.FIG. 11A shows an exemplary a single component articular surface repairsystem 1100 with varying curvature and radii. In this case, thearticular surface repair system is chosen to include convex and concaveportions. Such devices can be preferable in a lateral femoral condyle orsmall joints such as the elbow joint. FIG. 11B depicts a multi-componentarticular surface repair system with a deep component 1110 that mirrorsthe shape of the subchondral bone and a superficial component 1105closely matching the shape and curvature of the surrounding normalcartilage 1115. The deep component 1110 and the superficial component1105 demonstrate varying curvatures and radii with convex and concaveportions.

FIGS. 12A and B show exemplary articular repair systems 100 having anouter contour matching the surrounding normal cartilage 200. The systemsare implanted into the underlying bone 300 using one or more pegs 150,175. The pegs may be porous-coated and may have flanges 125 as shown inFIG. 12B.

FIG. 13 shows an example of a surgical tool 410 having one surface 400matching the geometry of an articular surface of the joint. Also shownis an aperture 415 in the tool 410 capable of controlling drill depthand width of the hole and allowing implantation of an insertion ofimplant 420 having a press-fit design.

FIG. 14 shows an exemplary articular repair device 500 including a flatsurface 510 to control depth and prevent toggle; an exterior surface 515having the contour of normal cartilage; flanges 517 to prevent rotationand control toggle; a groove 520 to facilitate tissue in-growth.

FIG. 15 depicts, in cross-section, an example of a surgical tool 600containing apertures 605 through which a surgical drill or saw can fitand which guide the drill or saw to make cuts or holes in the bone 610.Dotted lines represent where the cuts corresponding to the apertureswill be made in bone.

FIG. 16 depicts, in cross-section, another example of a surgical tool620 containing an aperture 625 through which a surgical drill or saw canfit. The aperture guides the drill or saw to make the proper hole or cutin the underlying bone 630. Dotted lines represent where the cutcorresponding to the aperture will be made in bone.

FIG. 17A-D depict, in cross-section, another example of an implant 640with multiple anchoring pegs 645. FIGS. 17B-D show variouscross-sectional representations of the pegs: FIG. 17B shows a peg havinga groove; FIG. 17C shows a peg with radially-extending arms that helpanchor the device in the underlying bone; and FIG. 17D shows a peg withmultiple grooves or flanges.

FIGS. 18A and B depict an overhead view of an exemplary implant 650 withmultiple anchoring pegs 655 and depict how the pegs are not necessarilylinearly aligned along the longitudinal axis of the device.

FIG. 19A-E depict an exemplary implant 660 having radially extendingarms 665. FIG. 19B-E are overhead views of the implant showing that theshape of the peg need not be conical.

DETAILED DESCRIPTION OF THE INVENTION

The current invention provides for methods and devices for integrationof cartilage replacement or regenerating materials.

Before describing the present invention in detail, it is to beunderstood that this invention is not limited to particular formulationsor process parameters as such may, of course, vary. It is also to beunderstood that the terminology used herein is for the purpose ofdescribing particular embodiments of the invention only, and is notintended to be limiting.

The practice of the present invention employs, unless otherwiseindicated, conventional methods of x-ray imaging and processing, x-raytomosynthesis, ultrasound including A-scan, B-scan and C-scan, computedtomography (CT scan), magnetic resonance imaging (MRI), opticalcoherence tomography, single photon emission tomography (SPECT) andpositron emission tomography (PET) within the skill of the art. Suchtechniques are explained fully in the literature. See, e.g., X-RayStructure Determination: A Practical Guide, 2nd Edition, editors Stoutand Jensen, 1989, John Wiley & Sons, publisher; Body CT: A PracticalApproach, editor Slone, 1999, McGraw-Hill publisher; X-ray Diagnosis: APhysician's Approach, editor Lam, 1998 Springer-Verlag, publisher; andDental Radiology: Understanding the X-Ray Image, editor LaetitiaBrocklebank 1997, Oxford University Press publisher.

All publications, patents and patent applications cited herein, whetherabove or below, are hereby incorporated by reference in their entirety.

It must be noted that, as used in this specification and the appendedclaims, the singular forms “a”, “an”, and “the” include pluralreferences unless the content clearly dictates otherwise. Thus, forexample, reference to “an implantation site” includes a one or more suchsites.

DEFINITIONS

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which the invention pertains. Although any methods andmaterials similar or equivalent to those described herein can be used inthe practice for testing of the present invention, the preferredmaterials and methods are described herein.

The term “arthritis” refers to a group of conditions characterized byprogressive deterioration of joints. Thus, the term encompasses a groupof different diseases including, but not limited to, osteoarthritis(OA), rheumatoid arthritis, seronegative spondyloarthropathies andposttraumatic joint deformity.

The term “articular” refers to any joint. Thus, “articular cartilage”refers to cartilage in a joint such as a knee, ankle, hip, etc. The term“articular surface” refers to a surface of an articulating bone that iscovered by cartilage. For example, in a knee joint several differentarticular surfaces are present, e.g. in the patella, the medial femoralcondyle, the lateral femoral condyle, the medial tibial plateau and thelateral tibial plateau.

The term “weight-bearing surface” refers to the contact area between twoopposing articular surfaces during activities of normal daily living,e.g., normal gait. The weight-bearing surface can be determined by anysuitable means, for example based on data published in the literature,e.g. anatomic studies. The weight-bearing surface can be determined bysuperimposing predetermined angles of flexion, extension, translation,tilting and rotation on anatomic models, e.g. of the femur and thetibia. Anatomic models can be generated with use of an imaging test.Biomotion analysis, for example using optoelectronic registration means(see also International Publication WO 02/22014) can also be used todefine the weight-bearing surface. Moreover, kinematic imaging testssuch as fluoroscopy or MRI of joint motion can be used to estimate theweight-bearing surface for different physical activities. Differentmodalities for determining the weight-bearing area such as 2D x-rayfluoroscopy and MRI can be merged in order to estimate theweight-bearing area. The weight-bearing area can be determined using anycurrent and future optical, electronic, imaging, or other means ofassessing joint motion.

The term “cartilage” or “cartilage tissue” as used herein is generallyrecognized in the art, and refers to a specialized type of denseconnective tissue comprising cells embedded in an extracellular matrix(ECM) (see, for example, Cormack, 1987, Ham's Histology, 9th Ed., J. B.Lippincott Co., pp. 266-272). The biochemical composition of cartilagediffers according to type. Several types of cartilage are recognized inthe art, including, for example, hyaline cartilage such as that foundwithin the joints, fibrous cartilage such as that found within themeniscus and costal regions, and elastic cartilage. Hyaline cartilage,for example, comprises chondrocytes surrounded by a dense ECM consistingof collagen, proteoglycans and water. Fibrocartilage can form in areasof hyaline cartilage, for example after an injury or, more typically,after certain types of surgery. The production of any type of cartilageis intended to fall within the scope of the invention.

Furthermore, although described primarily in relation to methods for usein humans, the invention may also be practiced so as repair cartilagetissue in any mammal in need thereof, including horses, dogs, cats,sheep, pigs, among others. The treatment of such animals is intended tofall within the scope of the invention.

The terms “articular repair system” and “articular surface repairsystem” include any system (including, for example, compositions,devices and techniques) to repair, to replace or to regenerate a portionof a joint or an entire joint. The term encompasses systems that repairarticular cartilage, articular bone or both bone and cartilage.Articular surface repair systems may also include a meniscal repairsystem (e.g., meniscal repair system can be composed of a biologic ornon-biologic material), for example a meniscal repair system havingbiomechanical and/or biochemical properties similar to that of healthymenisci. See, for example, U.S. Pat. Publication No. b 2002/0,022,884A1.The meniscal repair system can be surgically or arthroscopicallyattached to the joint capsule or one or more ligaments. Non-limitingexamples of repair systems include metal or plastic implants, polymerimplants, combinations thereof, injectable repair materials, for examplematerials that are self-hardening, autologous chondrocytetransplantation, osteochondral allografting, osteochondral autografting,tibial corticotomy, femoral and/or tibial osteotomy. Repair systems alsoinclude treatment with cartilage or bone tissue grown ex vivo as well asin vivo, stem cells, cartilage material grown with use of stem cells,fetal cells or immature or mature cartilage cells, an artificialnon-human material, an agent that stimulates repair of diseasedcartilage tissue, an agent that stimulates growth of cells, an agentthat protects diseased cartilage tissue and that protects adjacentnormal cartilage tissue. Articular repair systems include also treatmentwith a cartilage tissue transplant, a cartilage tissue graft, acartilage tissue implant, a cartilage tissue scaffold, or any othercartilage tissue replacement or regenerating material. Articular repairsystems may include also treatment with a bone tissue transplant, a bonetissue graft, a bone tissue implant, a bone tissue scaffold, or anyother bone tissue replacement or regenerating material. Articular repairsystems may also include treatment with a meniscus tissue transplant, ameniscus tissue graft, a meniscus tissue implant, a meniscus tissuescaffold, or any other meniscus tissue replacement or regeneratingmaterial. Articular repair systems include also surgical tools thatfacilitate the surgical procedure required for articular repair, forexample tools that prepare the area of diseased cartilage tissue and/orsubchondral bone for receiving, for example, a cartilage tissuereplacement or regenerating material. The term “non-pliable” refers tomaterial that cannot be significantly bent but may retain elasticity.

The terms “replacement material” or “regenerating material” include abroad range of natural and/or synthetic materials including metals,metal alloys, polymers, injectables, combinations thereof used in themethods described herein, for example, cartilage or bone tissue grown exvivo or in vivo, stem cells, cartilage material grown from stem cells,stem cells, fetal cell, immature or mature cartilage cells, an agentthat stimulates growth of cells, an artificial non-human material, atissue transplant, a tissue graft, a tissue implant, a tissue scaffold,or a tissue regenerating material. The term includes biologicalmaterials isolated from various sources (e.g., cells) as well asmodified (e.g., genetically modified) materials and/or combinations ofisolated and modified materials.

The term “imaging test” includes, but is not limited to, x-ray basedtechniques (such as conventional film based x-ray films, digital x-rayimages, single and dual x-ray absorptiometry, radiographicabsorptiometry); fluoroscopic imaging, for example with C-arm devicesincluding C-arm devices with tomographic or cross-sectional imagingcapability, digital x-ray tomosynthesis, x-ray imaging including digitalx-ray tomosynthesis with use of x-ray contrast agents, for example afterintra-articular injection, ultrasound including broadband ultrasoundattenuation measurement and speed of sound measurements, A-scan, B-scanand C-scan; computed tomography; nuclear scintigraphy; SPECT; positronemission tomography, optical coherence tomography and MRI. One or moreof these imaging tests may be used in the methods described herein, forexample in order to obtain certain morphological information about oneor several tissues such as bone including bone mineral density andcurvature of the subchondral bone, cartilage including biochemicalcomposition of cartilage, cartilage thickness, cartilage volume,cartilage curvature, size of an area of diseased cartilage, severity ofcartilage disease or cartilage loss, marrow including marrowcomposition, synovium including synovial inflammation, lean and fattytissue, and thickness, dimensions and volume of soft and hard tissues.The imaging test can be performed with use of a contrast agent, such asGd-DTPA in the case of MRI.

The term “A-scan” refers to an ultrasonic technique where an ultrasonicsource transmits an ultrasonic wave into an object, such as patient'sbody, and the amplitude of the returning echoes (signals) are recordedas a function of time. Only structures that lie along the direction ofpropagation are interrogated. As echoes return from interfaces withinthe object or tissue, the transducer crystal produces a voltage that isproportional to the echo intensity. The sequence of signal acquisitionand processing of the A-scan data in a modern ultrasonic instrumentusually occurs in six major steps:

(1) Detection of the echo (signal) occurs via mechanical deformation ofthe piezoelectric crystal and is converted to an electric signal havinga small voltage.

(2) Preamplification of the electronic signal from the crystal, into amore useful range of voltages is usually necessary to ensure appropriatesignal processing.

(3) Time Gain Compensation compensates for the attenuation of theultrasonic signal with time, which arises from travel distance. Timegain compensation may be user-adjustable and may be changed to meet theneeds of the specific application. Usually, the ideal time gaincompensation curve corrects the signal for the depth of the reflectiveboundary. Time gain compensation works by increasing the amplificationfactor of the signal as a function of time after the ultrasonic pulsehas been emitted. Thus, reflective boundaries having equal abilities toreflect ultrasonic waves will have equal ultrasonic signals, regardlessof the depth of the boundary.

(4) Compression of the time compensated signal can be accomplished usinglogarithmic amplification to reduce the large dynamic range (range ofsmallest to largest signals) of the echo amplitudes. Small signals aremade larger and large signals are made smaller. This step provides aconvenient scale for display of the amplitude variations on the limitedgray scale range of a monitor.

(5) Rectification, demodulation and envelope detection of the highfrequency electronic signal permits the sampling and digitization of theecho amplitude free of variations induced by the sinusoidal nature ofthe waveform.

(6) Rejection level adjustment sets the threshold of signal amplitudesthat are permitted to enter a data storage, processing or displaysystem. Rejection of lower signal amplitudes reduces noise levels fromscattered ultrasonic signals.

The term “B-scan” refers to an ultrasonic technique where the amplitudeof the detected returning echo is recorded as a function of thetransmission time, the relative location of the detector in the probeand the signal amplitude. This is often represented by the brightness ofa visual element, such as a pixel, in a two-dimensional image. Theposition of the pixel along the y-axis represents the depth, i.e. halfthe time for the echo to return to the transducer (for one half of thedistance traveled). The position along the x-axis represents thelocation of the returning echoes relative to the long axis of thetransducer, i.e. the location of the pixel either in a superoinferior ormediolateral direction or a combination of both. The display of multipleadjacent scan lines creates a composite two-dimensional image thatportrays the general contour of internal organs.

The term “C-scan” refers to an ultrasonic technique where additionalgating electronics are incorporated into a B-scan to eliminateinterference from underlying or overlying structures by scanning at aconstant-depth. An interface reflects part of the ultrasonic beamenergy. All interfaces along the scan line may contribute to themeasurement. The gating electronics of the C-mode rejects all returningechoes except those received during a specified time interval. Thus,only scan data obtained from a specific depth range are recorded.Induced signals outside the allowed period are not amplified and, thus,are not processed and displayed. C-mode-like methods are also describedherein for A-scan techniques and devices in order to reduce theprobe/skin interface reflection. The term “repair” is used in a broadsense to refer to one or more repairs to damaged joints (e.g., cartilageor bone) or to replacement of one or more components or regions of thejoint. Thus, the term encompasses both repair (e.g., one or moreportions of a cartilage and/or layers of cartilage or bone) andreplacement (e.g., of an entire cartilage).

The term “C-arm” refers to a fluoroscopic x-ray system mounted on aC-shaped arch that allows it to rotate and/or tilt passively or activelyaround the object to be imaged. The x-ray beam that is transmitted bythe x-ray source through the object and received by the detector isdisplayed on a screen. C-arm typically includes systems that havecross-sectional imaging capability, for example by using rotation of thex-ray tube and detector to reconstruct a cross-sectional image similarto a CT rather than a conventional projectional x-ray only.

The terms “hardening,” “solidifying,” and “curable” refers to any liquidor sufficiently flowable material that forms a solid or gel, either overtime, upon contact with another substance and/or upon application ofenergy.

General Overview

The present invention provides methods and compositions for repairingjoints, particularly for repairing articular cartilage and forfacilitating the integration of a wide variety of cartilage repairmaterials into a subject. Among other things, the techniques describedherein allow for the customization of cartilage repair material to suita particular subject, for example in terms of size, cartilage thicknessand/or curvature. When the shape (e.g., size, thickness and/orcurvature) of the articular cartilage surface is an exact or nearanatomic fit with the non-damaged cartilage or with the subject'soriginal cartilage, the success of repair is enhanced. The repairmaterial may be shaped prior to implantation and such shaping can bebased, for example, on electronic images that provide informationregarding curvature or thickness of any “normal” cartilage surroundingthe defect and/or on curvature of the bone underlying the defect. Thus,the current invention provides, among other things, for minimallyinvasive methods for partial joint replacement. The methods will requireonly minimal or, in some instances, no loss in bone stock. Additionally,unlike with current techniques, the methods described herein will helpto restore the integrity of the articular surface by achieving an exactor near anatomic match between the implant and the surrounding oradjacent cartilage and/or subchondral bone.

Advantages of the present invention can include, but are not limited to,(i) customization of joint repair, thereby enhancing the efficacy andcomfort level for the patient following the repair procedure; (ii)eliminating the need for a surgeon to measure the defect to be repairedintraoperatively in some embodiments; (iii) eliminating the need for asurgeon to shape the material during the implantation procedure; (iv)providing methods of evaluating curvature of the repair material basedon bone or tissue images or based on intraoperative probing techniques;(v) providing methods of repairing joints with only minimal or, in someinstances, no loss in bone stock; and (vi) improving postoperative jointcongruity.

Thus, the methods described herein allow for the design and use of jointrepair material that more precisely fits the defect (e.g., site ofimplantation) and, accordingly, provides improved repair of the joint.

1.0. Assessment of Defects

The methods and compositions described herein may be used to treatdefects resulting from disease of the cartilage (e.g., osteoarthritis),bone damage, cartilage damage, trauma, and/or degeneration due tooveruse or age. The invention allows, among other things, a healthpractitioner to evaluate and treat such defects. The size, volume andshape of the area of interest may include only the region of cartilagethat has the defect, but preferably will also include contiguous partsof the cartilage surrounding the cartilage defect.

Size, curvature and/or thickness measurements can be obtained using anysuitable techniques, for example in one direction, two directions,and/or in three dimensions for example, using suitable mechanical means,laser devices, molds, materials applied to the articular surface thatharden and “memorize the surface contour,” and/or one or more imagingtechniques. Measurements may be obtained non-invasively and/orintraoperatively (e.g., using a probe or other surgical device).

1.1. Imaging Techniques

Non-limiting examples of imaging techniques suitable for measuringthickness and/or curvature (e.g., of cartilage and/or bone) or size ofareas of diseased cartilage or cartilage loss include the use of x-rays,magnetic resonance imaging (MRI), computed tomography scanning (CT, alsoknown as computerized axial tomography or CAT), optical coherencetomography, SPECT, PET, ultrasound imaging techniques, and opticalimaging techniques. (See, also, International Patent Publication WO02/22014; U.S. Pat. No. 6,373,250 and Vandeberg et al. (2002) Radiology222:430-436).

In certain embodiments, CT or MRI is used to assess tissue, bone,cartilage and any defects therein, for example cartilage lesions orareas of diseased cartilage, to obtain information on subchondral boneor cartilage degeneration and to provide morphologic or biochemical orbiomechanical information about the area of damage. Specifically,changes such as fissuring, partial or full thickness cartilage loss, andsignal changes within residual cartilage can be detected using one ormore of these methods. For discussions of the basic NMR principles andtechniques, see MRI Basic Principles and Applications, Second Edition,Mark A. Brown and Richard C. Semelka, Wiley-Liss, Inc. (1999). For adiscussion of MRI including conventional T1 and T2-weighted spin-echoimaging, gradient recalled echo (GRE) imaging, magnetization transfercontrast (MTC) imaging, fast spin-echo (FSE) imaging, contrast enhancedimaging, rapid acquisition relaxation enhancement, (RARE) imaging,gradient echo acquisition in the steady state, (GRASS), and drivenequilibrium Fourier transform (DEFT) imaging, to obtain information oncartilage, see WO 02/22014. Thus, in preferred embodiments, themeasurements are three-dimensional images obtained as described in WO02/22014. Three-dimensional internal images, or maps, of the cartilagealone or in combination with a movement pattern of the joint can beobtained. Three-dimensional internal images can include information onbiochemical composition of the articular cartilage. In addition, imagingtechniques can be compared over time, for example to provide up to dateinformation on the shape and type of repair material needed.

Any of the imaging devices described herein may also be usedintra-operatively (see, also below), for example using a hand-heldultrasound and/or optical probe to image the articular surfaceintra-operatively.

1.2. Intra-Operative Measurements

Alternatively, or in addition to, non-invasive imaging techniques,measurements of the size of an area of diseased cartilage or an area ofcartilage loss, measurements of cartilage thickness and/or curvature ofcartilage or bone can be obtained intraoperatively during arthroscopy oropen arthrotomy. Intraoperative measurements may or may not involveactual contact with one or more areas of the articular surfaces.

Devices to obtain intraoperative measurements of cartilage, and togenerate a topographical map of the surface include but are not limitedto, Placido disks and laser interferometers, and/or deformablematerials. (See, for example, U.S. Pat. Nos. 6,382,028; 6,057,927;5,523,843; 5,847,804; and 5,684,562). For example, a Placido disk (aconcentric array that projects well-defined circles of light of varyingradii, generated either with laser or white light transported viaoptical fiber) can be attached to the end of an endoscopic device (or toany probe, for example a hand-held probe) so that the circles of lightare projected onto the cartilage surface. One or more imaging camerascan be used (e.g., attached to the device) to capture the reflection ofthe circles. Mathematical analysis is used to determine the surfacecurvature. The curvature can then be visualized on a monitor as acolor-coded, topographical map of the cartilage surface. Additionally, amathematical model of the topographical map can be used to determine theideal surface topography to replace any cartilage defects in the areaanalyzed. This computed, ideal surface can then also be visualized onthe monitor, and is used to select the curvature of the replacementmaterial or regenerating material.

Similarly a laser interferometer can also be attached to the end of anendoscopic device. In addition, a small sensor may be attached to thedevice in order to determine the cartilage surface curvature using phaseshift interferometry, producing a fringe pattern analysis phase map(wave front) visualization of the cartilage surface. The curvature canthen be visualized on a monitor as a color coded, topographical map ofthe cartilage surface. Additionally, a mathematical model of thetopographical map can be used to determine the ideal surface topographyto replace any cartilage defects in the area analyzed. This computed,ideal surface can then also be visualized on the monitor, and can beused to select the curvature of the replacement cartilage.

One skilled in the art will readily recognize other techniques foroptical measurements of the cartilage surface curvature.

Mechanical devices (e.g., probes) may also be used for intraoperativemeasurements, for example, deformable materials such as gels, molds, anyhardening materials (e.g., materials that remain deformable until theyare heated, cooled, or otherwise manipulated). See, e.g., WO 02/34310.For example, a deformable gel can be applied to a femoral condyle. Theside of the gel pointing towards the condyle will yield a negativeimpression of the surface contour of the condyle. Said negativeimpression can be used to determine the size of a defect, the depth of adefect and the curvature of the articular surface in and adjacent to adefect. This information can be used to select a therapy, e.g. anarticular surface repair system. In another example, a hardeningmaterial can be applied to an articular surface, e.g. a femoral condyleor a tibial plateau. Said hardening material will remain on thearticular surface until hardening has occurred. The hardening materialwill then be removed from the articular surface. The side of thehardening material pointing towards the articular surface will yield anegative impression of the articular surface. The negative impressioncan be used to determine the size of a defect, the depth of a defect andthe curvature of the articular surface in and adjacent to a defect. Thisinformation can be used to select a therapy, e.g. an articular surfacerepair system.

In certain embodiments, the deformable material comprises a plurality ofindividually moveable mechanical elements. When pressed against thesurface of interest, each element may be pushed in the opposingdirection and the extent to which it is pushed (deformed) willcorrespond to the curvature of the surface of interest. The device mayinclude a brake mechanism so that the elements are maintained in theposition that mirrors the surface of the cartilage and/or bone. Thedevice can then be removed from the patient and analyzed for curvature.Alternatively, each individual moveable element may include markersindicating the amount and/or degree they are deformed at a given spot. Acamera can be used to intra-operatively image the device and the imagecan be saved and analyzed for curvature information. Suitable markersinclude, but are not limited to, actual linear measurements (metric orimperial), different colors corresponding to different amounts ofdeformation and/or different shades or hues of the same color(s).

Other devices to measure cartilage and subchondral bone intraoperativelyinclude, for example, ultrasound probes. An ultrasound probe, preferablyhandheld, can be applied to the cartilage and the curvature of thecartilage and/or the subchondral bone can be measured. Moreover, thesize of a cartilage defect can be assessed and the thickness of thearticular cartilage can be determined. Such ultrasound measurements canbe obtained in A-mode, B-mode, or C-mode. If A-mode measurements areobtained, an operator will typically repeat the measurements withseveral different probe orientations, e.g. mediolateral andanteroposterior, in order to derive a three-dimensional assessment ofsize, curvature and thickness.

One skilled in the art will easily recognize that different probedesigns are possible using said optical, laser interferometry,mechanical and ultrasound probes. The probes are preferably handheld. Incertain embodiments, the probes or at least a portion of the probe,typically the portion that is in contact with the tissue, will besterile. Sterility can be achieved with use of sterile covers, forexample similar to those disclosed in WO9908598A1.

Analysis on the curvature of the articular cartilage or subchondral boneusing imaging tests and/or intraoperative measurements can be used todetermine the size of an area of diseased cartilage or cartilage loss.For example, the curvature can change abruptly in areas of cartilageloss. Such abrupt or sudden changes in curvature can be used to detectthe boundaries of diseased cartilage or cartilage defects.

1.3. Models

Using information on thickness and curvature of the cartilage, aphysical model of the surfaces of the articular cartilage and of theunderlying bone can be created. This physical model can berepresentative of a limited area within the joint or it can encompassthe entire joint. For example, in the knee joint, the physical model canencompass only the medial or lateral femoral condyle, both femoralcondyles and the notch region, the medial tibial plateau, the lateraltibial plateau, the entire tibial plateau, the medial patella, thelateral patella, the entire patella or the entire joint. The location ofa diseased area of cartilage can be determined, for example using a 3Dcoordinate system or a 3D Euclidian distance as described in WO02/22014.

In this way, the size of the defect to be repaired can be determined. Aswill be apparent, some, but not all, defects will include less than theentire cartilage. Thus, in one embodiment of the invention, thethickness of the normal or only mildly diseased cartilage surroundingone or more cartilage defects is measured. This thickness measurementcan be obtained at a single point or, preferably, at multiple points,for example 2 point, 4-6 points, 7-10 points, more than 10 points orover the length of the entire remaining cartilage. Furthermore, once thesize of the defect is determined, an appropriate therapy (e.g.,articular repair system) can be selected such that as much as possibleof the healthy, surrounding tissue is preserved.

In other embodiments, the curvature of the articular surface can bemeasured to design and/or shape the repair material. Further, both thethickness of the remaining cartilage and the curvature of the articularsurface can be measured to design and/or shape the repair material.Alternatively, the curvature of the subchondral bone can be measured andthe resultant measurement(s) can be used to either select or shape acartilage replacement material.

2.0. Repair Materials

A wide variety of materials find use in the practice of the presentinvention, including, but not limited to, plastics, metals, ceramics,biological materials (e.g., collagen or other extracellular matrixmaterials), hydroxyapatite, cells (e.g., stem cells, chondrocyte cellsor the like), or combinations thereof. Based on the information (e.g.,measurements) obtained regarding the defect and the articular surfaceand/or the subchondral bone, a repair material can be formed orselected. Further, using one or more of these techniques describedherein, a cartilage replacement or regenerating material having acurvature that will fit into a particular cartilage defect, will followthe contour and shape of the articular surface, and will match thethickness of the surrounding cartilage. The repair material may includeany combination of materials, and preferably includes at least onenon-pliable (hard) material.

2.1. Metal and Polymeric Repair Materials

Currently, joint repair systems often employ metal and/or polymericmaterials including, for example, prosthesis which are anchored into theunderlying bone (e.g., a femur in the case of a knee prosthesis). See,e.g., U.S. Pat. Nos. 6,203,576 and 6,322,588 and references citedtherein. A wide-variety of metals may find use in the practice of thepresent invention, and may be selected based on any criteria, forexample, based on resiliency to impart a desired degree of rigidity.Non-limiting examples of suitable metals include silver, gold, platinum,palladium, iridium, copper, tin, lead, antimony, bismuth, zinc,titanium, cobalt, stainless steel, nickel, iron alloys, cobalt alloys,such as Elgiloy®, a cobalt-chromium-nickel alloy, and MP35N, anickel-cobalt-chromium-molybdenum alloy, and Nitinol™, a nickel-titaniumalloy, aluminum, manganese, iron, tantalum, other metals that can slowlyform polyvalent metal ions, for example to inhibit calcification ofimplanted substrates in contact with a patient's bodily fluids ortissues, and combinations thereof.

Suitable synthetic polymers include, without limitation, polyamides(e.g., nylon), polyesters, polystyrenes, polyacrylates, vinyl polymers(e.g., polyethylene, polytetrafluoroethylene, polypropylene andpolyvinyl chloride), polycarbonates, polyurethanes, poly dimethylsiloxanes, cellulose acetates, polymethyl methacrylates, polyether etherketones, ethylene vinyl acetates, polysulfones, nitrocelluloses, similarcopolymers and mixtures thereof. Bioresorbable synthetic polymers canalso be used such as dextran, hydroxyethyl starch, derivatives ofgelatin, polyvinylpyrrolidone, polyvinyl alcohol,poly[N-(2-hydroxypropyl-) methacrylamide], poly(hydroxy acids),poly(epsilon-caprolactone), polylactic acid, polyglycolic acid,poly(dimethyl glycolic acid), poly(hydroxy butyrate), and similarcopolymers may also be used.

The polymers can be prepared by any of a variety of approaches includingconventional polymer processing methods. Preferred approaches include,for example, injection molding, which is suitable for the production ofpolymer components with significant structural features, and rapidprototyping approaches, such as reaction injection molding andstereo-lithography. The substrate can be textured or made porous byeither physical abrasion or chemical alteration to facilitateincorporation of the metal coating.

More than one metal and/or polymer may be used in combination with eachother. For example, one or more metal-containing substrates may becoated with polymers in one or more regions or, alternatively, one ormore polymer-containing substrate may be coated in one or more regionswith one or more metals.

The system or prosthesis can be porous or porous coated. The poroussurface components can be made of various materials including metals,ceramics, and polymers. These surface components can, in turn, besecured by various means to a multitude of structural cores formed ofvarious metals. Suitable porous coatings include, but are not limitedto, metal, ceramic, polymeric (e.g., biologically neutral elastomerssuch as silicone rubber, polyethylene terephthalate and/or combinationsthereof) or combinations thereof. See, e.g., Hahn U.S. Pat. No.3,605,123. Tronzo U.S. Pat. No. 3,808,606 and Tronzo U.S. Pat. No.3,843,975; Smith U.S. Pat. No. 3,314,420; Scharbach U.S. Pat. No.3,987,499; and German Offenlegungsschrift 2,306,552. There may be morethan one coating layer and the layers may have the same or differentporosities. See, e.g., U.S. Pat. No. 3,938,198.

The coating may be applied by surrounding a core with powdered polymerand heating until cured to form a coating with an internal network ofinterconnected pores. The tortuosity of the pores (e.g., a measure oflength to diameter of the paths through the pores) may be important inevaluating the probable success of such a coating in use on a prostheticdevice. See, also, Morris U.S. Pat. No. 4,213,816. The porous coatingmay be applied in the form of a powder and the article as a wholesubjected to an elevated temperature that bonds the powder to thesubstrate. Selection of suitable polymers and/or powder coatings may bedetermined in view of the teachings and references cited herein, forexample based on the melt index of each.

2.2. Biological Repair Materials

Repair materials may also include one or more biological material eitheralone or in combination with non-biological materials. For example, anybase material can be designed or shaped and suitable cartilagereplacement or regenerating material(s) such as fetal cartilage cellscan be applied to be the base. The cells can be then be grown inconjunction with the base until the thickness (and/or curvature) of thecartilage surrounding the cartilage defect has been reached. Conditionsfor growing cells (e.g., chondrocytes) on various substrates in culture,ex vivo and in vivo are described, for example, in U.S. Pat. Nos.5,478,739; 5,842,477; 6,283,980 and 6,365,405. Non-limiting examples ofsuitable substrates include plastic, tissue scaffold, a bone replacementmaterial (e.g., a hydroxyapatite, a bioresorbable material), or anyother material suitable for growing a cartilage replacement orregenerating material on it.

Biological polymers can be naturally occurring or produced in vitro byfermentation and the like. Suitable biological polymers include, withoutlimitation, collagen, elastin, silk, keratin, gelatin, polyamino acids,cat gut sutures, polysaccharides (e.g., cellulose and starch) andmixtures thereof. Biological polymers may be bioresorbable.

Biological materials used in the methods described herein can beautografts (from the same subject); allografts (from another individualof the same species) and/or xenografts (from another species). See,also, International Patent Publications WO 02/22014 and WO 97/27885. Incertain embodiments autologous materials are preferred, as they maycarry a reduced risk of immunological complications to the host,including re-absorption of the materials, inflammation and/or scarringof the tissues surrounding the implant site.

In one embodiment of the invention, a probe is used to harvest tissuefrom a donor site and to prepare a recipient site. The donor site can belocated in a xenograft, an allograft or an autograft. The probe is usedto achieve a good anatomic match between the donor tissue sample and therecipient site. The probe is specifically designed to achieve a seamlessor near seamless match between the donor tissue sample and the recipientsite. The probe can, for example, be cylindrical. The distal end of theprobe is typically sharp in order to facilitate tissue penetration.Additionally, the distal end of the probe is typically hollow in orderto accept the tissue. The probe can have an edge at a defined distancefrom its distal end, e.g. at 1 cm distance from the distal end and theedge can be used to achieve a defined depth of tissue penetration forharvesting. The edge can be external or can be inside the hollow portionof the probe. For example, an orthopedic surgeon can take the probe andadvance it with physical pressure into the cartilage, the subchondralbone and the underlying marrow in the case of a joint such as a kneejoint. The surgeon can advance the probe until the external or internaledge reaches the cartilage surface. At that point, the edge will preventfurther tissue penetration thereby achieving a constant and reproducibletissue penetration. The distal end of the probe can include a blade orsaw-like structure or tissue cutting mechanism. For example, the distalend of the probe can include an iris-like mechanism consisting ofseveral small blades. The at least one or more blades can be moved usinga manual, motorized or electrical mechanism thereby cutting through thetissue and separating the tissue sample from the underlying tissue.Typically, this will be repeated in the donor and the recipient. In thecase of an iris-shaped blade mechanism, the individual blades can bemoved so as to close the iris thereby separating the tissue sample fromthe donor site.

In another embodiment of the invention, a laser device or aradiofrequency device can be integrated inside the distal end of theprobe. The laser device or the radiofrequency device can be used to cutthrough the tissue and to separate the tissue sample from the underlyingtissue.

In one embodiment of the invention, the same probe can be used in thedonor and in the recipient. In another embodiment, similarly shapedprobes of slightly different physical dimensions can be used. Forexample, the probe used in the recipient can be slightly smaller thanthat used in the donor thereby achieving a tight fit between the tissuesample or tissue transplant and the recipient site. The probe used inthe recipient can also be slightly shorter than that used in the donorthereby correcting for any tissue lost during the separation or cuttingof the tissue sample from the underlying tissue in the donor material.

Any biological repair material may be sterilized to inactivatebiological contaminants such as bacteria, viruses, yeasts, molds,mycoplasmas and parasites. Sterilization may be performed using anysuitable technique, for example radiation, such as gamma radiation.

Any of the biological material described herein may be harvested withuse of a robotic device. The robotic device can use information from anelectronic image for tissue harvesting.

In certain embodiments, the cartilage replacement material has aparticular biochemical composition. For instance, the biochemicalcomposition of the cartilage surrounding a defect can be assessed bytaking tissue samples and chemical analysis or by imaging techniques.For example, WO 02/22014 describes the use of gadolinium for imaging ofarticular cartilage to monitor glycosaminoglycan content within thecartilage. The cartilage replacement or regenerating material can thenbe made or cultured in a manner, to achieve a biochemical compositionsimilar to that of the cartilage surrounding the implantation site. Theculture conditions used to achieve the desired biochemical compositionscan include, for example, varying concentrations biochemical compositionof said cartilage replacement or regenerating material can, for example,be influenced by controlling concentrations and exposure times ofcertain nutrients and growth factors.

2.3. Multiple-Component Repair Materials

The articular repair system may include one or more components.Non-limiting examples of one-component systems include a plastic, apolymer, a metal, a metal alloy, a biologic material or combinationsthereof. In certain embodiments, the surface of the repair system facingthe underlying bone is smooth. In other embodiments, the surface of therepair system facing the underlying bone is porous or porous-coated. Inanother aspect, the surface of the repair system facing the underlyingbone is designed with one or more grooves, for example to facilitate thein-growth of the surrounding tissue. The external surface of the devicecan have a step-like design, which can be advantageous for alteringbiomechanical stresses. Optionally, flanges can also be added at one ormore positions on the device (e.g., to prevent the repair system fromrotating, to control toggle and/or prevent settling into the marrowcavity). The flanges can be part of a conical or a cylindrical design. Aportion or all of the repair system facing the underlying bone can alsobe flat which may help to control depth of the implant and to preventtoggle. (See, also FIGS. 12, 13 and 14).

Non-limiting examples of multiple-component systems include combinationsof metal, plastic, metal alloys and one or more biological materials.One or more components of the articular surface repair system can becomposed of a biologic material (e.g. a tissue scaffold with cells suchas cartilage cells or stem cells alone or seeded within a substrate suchas a bioresorable material or a tissue scaffold, allograft, autograft orcombinations thereof) and/or a non-biological material (e.g.,polyethylene or a chromium alloy such as chromium cobalt).

Thus, the repair system can include one or more areas of a singlematerial or a combination of materials, for example, the articularsurface repair system can have a superficial and a deep component. Thesuperficial component is typically designed to have size, thickness andcurvature similar to that of the cartilage tissue lost while the deepcomponent is typically designed to have a curvature similar to thesubchondral bone. In addition, the superficial component can havebiomechanical properties similar to articular cartilage, including butnot limited to similar elasticity and resistance to axial loading orshear forces. The superficial and the deep component can consist of twodifferent metals or metal alloys. One or more components of the system(e.g., the deep portion) can be composed of a biologic materialincluding, but not limited to bone, or a non-biologic materialincluding, but not limited to hydroxyapatite, tantalum, a chromiumalloy, chromium cobalt or other metal alloys.

One or more regions of the articular surface repair system (e.g., theouter margin of the superficial portion and/or the deep portion) can bebioresorbable, for example to allow the interface between the articularsurface repair system and the patient's normal cartilage, over time, tobe filled in with hyaline or fibrocartilage. Similarly, one or moreregions (e.g., the outer margin of the superficial portion of thearticular surface repair system and/or the deep portion) can be porous.The degree of porosity can change throughout the porous region, linearlyor non-linearly, for where the degree of porosity will typicallydecrease towards the center of the articular surface repair system. Thepores can be designed for in-growth of cartilage cells, cartilagematrix, and connective tissue thereby achieving a smooth interfacebetween the articular surface repair system and the surroundingcartilage.

The repair system (e.g., the deep component in multiple componentsystems) can be attached to the patient's bone with use of a cement-likematerial such as methylmethacrylate, injectable hydroxy- orcalcium-apatite materials and the like.

In certain embodiments, one or more portions of the articular surfacerepair system can be pliable or liquid or deformable at the time ofimplantation and can harden later. Hardening can occur within 1 secondto 2 hours (or any time period therebetween), preferably with in 1second to 30 minutes (or any time period therebetween), more preferablybetween 1 second and 10 minutes (or any time period therebetween).

One or more components of the articular surface repair system can beadapted to receive injections. For example, the external surface of thearticular surface repair system can have one or more openings therein.The openings can be sized so as to receive screws, tubing, needles orother devices which can be inserted and advanced to the desired depth,for example through the articular surface repair system into the marrowspace. Injectables such as methylmethacrylate and injectable hydroxy- orcalcium-apatite materials can then be introduced through the opening (ortubing inserted therethrough) into the marrow space thereby bonding thearticular surface repair system with the marrow space. Similarly, screwsor pins can be inserted into the openings and advanced to the underlyingsubchondral bone and the bone marrow or epiphysis to achieve fixation ofthe articular surface repair system to the bone. Portions or allcomponents of the screw or pin can be bioresorbable, for example, thedistal portion of a screw that protrudes into the marrow space can bebioresorbable. During the initial period after the surgery, the screwcan provide the primary fixation of the articular surface repair system.Subsequently, ingrowth of bone into a porous coated area along theundersurface of the articular cartilage repair system can take over asthe primary stabilizer of the articular surface repair system againstthe bone.

The articular surface repair system can be anchored to the patient'sbone with use of a pin or screw or other attachment mechanism. Theattachment mechanism can be bioresorbable. The screw or pin orattachment mechanism can be inserted and advanced towards the articularsurface repair system from a non-cartilage covered portion of the boneor from a non-weight-bearing surface of the joint.

The interface between the articular surface repair system and thesurrounding normal cartilage can be at an angle, for example oriented atan angle of 90 degrees relative to the underlying subchondral bone.Suitable angles can be determined in view of the teachings herein, andin certain cases, non-90 degree angles may have advantages with regardto load distribution along the interface between the articular surfacerepair system and the surrounding normal cartilage.

The interface between the articular surface repair system and thesurrounding normal cartilage and/or bone may be covered with apharmaceutical or bioactive agent, for example a material thatstimulates the biological integration of the repair system into thenormal cartilage and/or bone. The surface area of the interface can beirregular, for example, to increase exposure of the interface topharmaceutical or bioactive agents.

2.4. Customized Containers

In another embodiment of the invention, a container or well can beformed to the selected specifications, for example to match the materialneeded for a particular subject or to create a stock of repair materialsin a variety of sizes. The size and shape of the container may bedesigned using the thickness and curvature information obtained from thejoint and from the cartilage defect. More specifically, the inside ofthe container can be shaped to follow any selected measurements, forexample as obtained from the cartilage defect(s) of a particularsubject. The container can be filled with a cartilage replacement orregenerating material, for example, collagen-containing materials,plastics, bioresorbable materials and/or any suitable tissue scaffold.The cartilage regenerating or replacement material can also consist of asuspension of stem cells or fetal or immature or mature cartilage cellsthat subsequently develop to more mature cartilage inside the container.Further, development and/or differentiation can be enhanced with use ofcertain tissue nutrients and growth factors.

The material is allowed to harden and/or grow inside the container untilthe material has the desired traits, for example, thickness, elasticity,hardness, biochemical composition, etc. Molds can be generated using anysuitable technique, for example computer devices and automation, e.g.computer assisted design (CAD) and, for example, computer assistedmodeling (CAM). Because the resulting material generally follows thecontour of the inside of the container it will better fit the defectitself and facilitate integration.

2.5. Shaping

In certain instances shaping of the repair material will be requiredbefore or after formation (e.g., growth to desired thickness), forexample where the thickness of the required cartilage material is notuniform (e.g., where different sections of the cartilage replacement orregenerating material require different thicknesses).

The replacement material can be shaped by any suitable techniqueincluding, but not limited to, mechanical abrasion, laser abrasion orablation, radiofrequency treatment, cryoablation, variations in exposuretime and concentration of nutrients, enzymes or growth factors and anyother means suitable for influencing or changing cartilage thickness.See, e.g., WO 00/15153; If enzymatic digestion is used, certain sectionsof the cartilage replacement or regenerating material can be exposed tohigher doses of the enzyme or can be exposed longer as a means ofachieving different thicknesses and curvatures of the cartilagereplacement or regenerating material in different sections of saidmaterial.

The material can be shaped manually and/or automatically, for exampleusing a device into which a pre-selected thickness and/or curvature hasbeen inputted and programming the device to achieve the desired shape.

In addition to, or instead of, shaping the cartilage repair material,the site of implantation (e.g., bone surface, any cartilage materialremaining, etc.) can also be shaped by any suitable technique in orderto enhanced integration of the repair material.

2.6. Pre-Existing Repair Systems

As described herein, repair systems of various sizes, curvatures andthicknesses can be obtained. These repair systems can be catalogued andstored to create a library of systems from which an appropriate systemcan then be selected. In other words, a defect is assessed in aparticular subject and a pre-existing repair system having the closestshape and size is selected from the library for further manipulation(e.g., shaping) and implantation.

2.7. Mini-Prosthesis

As noted above, the methods and compositions described herein can beused to replace only a portion of the articular surface, for example, anarea of diseased cartilage or lost cartilage on the articular surface.In these systems, the articular surface repair system may be designed toreplace only the area of diseased or lost cartilage or it can extendbeyond the area of diseased or lost cartilage, e.g., 3 or 5 mm intonormal adjacent cartilage. In certain embodiments, the prosthesisreplaces less than about 70% to 80% (or any value therebetween) of thearticular surface (e.g., any given articular surface such as a singlefemoral condyle, etc.), preferably, less than about 50% to 70% (or anyvalue therebetween), more preferably, less than about 30% to 50% (or anyvalue therebetween), more preferably less than about 20% to 30% (or anyvalue therebetween), even more preferably less than about 20% of thearticular surface.

As noted above, the prosthesis may include multiple components, forexample a component that is implanted into the bone (e.g., a metallicdevice) attached to a component that is shaped to cover the defect ofthe cartilage overlaying the bone. Additional components, for exampleintermediate plates, meniscus repairs systems and the like may also beincluded. It is contemplated that each component replaces less than allof the corresponding articular surface. However, each component need notreplace the same portion of the articular surface. In other words, theprosthesis may have a bone-implanted component that replaces less than30% of the bone and a cartilage component that replaces 60% of thecartilage. The prosthesis may include any combination, so long as eachcomponent replaces less than the entire articular surface.

The articular surface repair system may be formed or selected so that itwill achieve a near anatomic fit or match with the surrounding oradjacent cartilage. Typically, the articular surface repair system isformed and/or selected so that its outer margin located at the externalsurface will be aligned with the surrounding or adjacent cartilage.

Thus, the articular repair system can be designed to replace theweight-bearing portion (or more or less than the weight bearing portion)of an articular surface, for example in a femoral condyle. Theweight-bearing surface refers to the contact area between two opposingarticular surfaces during activities of normal daily living (e.g.,normal gait). At least one or more weight-bearing portions can bereplaced in this manner, e.g., on a femoral condyle and on a tibia.

In other embodiments, an area of diseased cartilage or cartilage losscan be identified in a weight-bearing area and only a portion of saidweight-bearing area, specifically the portion containing said diseasedcartilage or area of cartilage loss, can be replaced with an articularsurface repair system.

In another embodiment, for example in patients with diffuse cartilageloss, the articular repair system can be designed to replace an areaslightly larger than the weight-bearing surface.

In certain aspects, the defect to be repaired is located only on onearticular surface, typically the most diseased surface. For example, ina patient with severe cartilage loss in the medial femoral condyle butless severe disease in the tibia, the articular surface repair systemcan only be applied to the medial femoral condyle. Preferably, in anymethods described herein, the articular surface repair system isdesigned to achieve an exact or a near anatomic fit with the adjacentnormal cartilage.

In other embodiments, more than one articular surface can be repaired.

The area(s) of repair will be typically limited to areas of diseasedcartilage or cartilage loss or areas slightly greater than the area ofdiseased cartilage or cartilage loss within the weight-bearingsurface(s).

The implant and/or the implant site can be sculpted to achieve a nearanatomic alignment between the implant and the implant site. In anotherembodiment of the invention, an electronic image is used to measure thethickness, curvature, or shape of the articular cartilage or thesubchondral bone, and/or the size of a defect, and an articular surfacerepair system is selected using this information. The articular surfacerepair system can be inserted arthroscopically. The articular surfacerepair system can have a single radius. More typically, however, thearticular surface repair system 1100 can have varying curvatures andradii within the same plane, e.g. anteroposterior or mediolateral orsuperoinferior or oblique planes, or within multiple planes. In thismanner, the articular surface repair system can be shaped to achieve anear anatomic alignment between the implant and the implant site. Thisdesign allows not only allows for different degrees of convexity orconcavity, but also for concave portions within a predominantly convexshape or vice versa 1100.

If a multiple component repair material has been selected, for examplewith a superficial component 1105 consisting of a polymeric material anda deep component 1110 consisting of a metal alloy, the superficialcomponent can be designed so that its thickness and curvature willclosely match that of the surrounding cartilage 1115. Thus, thesuperficial component can have more than one thickness in differentportions of the articular repair system. Moreover, the superficialcomponent can have varying curvatures and radii within the same plane,e.g. anteroposterior or mediolateral or superoinferior or obliqueplanes, or within multiple planes. Similarly, the deep component canhave varying curvatures and radii within the same plane, e.g.anteroposterior or mediolateral or superoinferior or oblique planes, orwithin multiple planes. Typically, the curvature of the deep componentwill be designed to follow that of the subchondral bone.

In another embodiment the articular surface repair system has afixturing stem, for example, as described in the Background of U.S. Pat.No. 6,224,632. The fixturing stem can have different shapes includingconical, rectangular, fin among others. The mating bone cavity istypically similarly shaped as the corresponding stem.

As shown in FIG. 12, the articular surface repair system 100 can beaffixed to the subchondral bone 300, with one or more fixturing stems(pegs) 150 extending through the subchondral plate into the marrowspace. In certain instances, this design may reduce the likelihood thatthe implant will settle deeper into the joint over time by restingportions of the implant against the subchondral bone. The fixturingstems or pegs can be of any shape, for example, cylindrical or conical.Optionally, the fixturing stems or pegs can have notches or openings toallow bone ingrowth. In addition, the fixturing stems or pegs can beporous coated for bone ingrowth. The fixturing stems or pegs can beaffixed to the bone using bone cement. An anchoring device can beaffixed to the fixturing stem or peg. The anchoring device can have anumbrella shape (e.g., radially expanding elements) with the widerportion pointing towards the subchondral bone and away from the peg. Theanchoring device can be advantageous for providing immediate fixation ofthe implant. The undersurface of the articular repair system facing thesubchondral bone can be textured or rough thereby increasing the contactsurface between the articular repair system and the subchondral bone.Alternatively, the undersurface of the articular repair system can beporous coated thereby allowing ingrowth. The surgeon can support theingrowth of bone by treating the subchondral bone with a rasp, typicallyto create a larger surface area and/or until bleeding from thesubchondral bone occurs.

In another embodiment, the articular surface repair system can beattached to the underlying bone or bone marrow using bone cement. Bonecement is typically made from an acrylic polymeric material. Typically,the bone cement is comprised of two components: a dry power componentand a liquid component, which are subsequently mixed together. The drycomponent generally includes an acrylic polymer, such aspolymethylmethacrylate (PMMA). The dry component can also contain apolymerization initiator such as benzoylperoxide, which initiates thefree-radical polymerization process that occurs when the bone cement isformed. The liquid component, on the other hand, generally contains aliquid monomer such as methyl methacrylate (MMA). The liquid componentcan also contain an accelerator such as an amine (e.g.,N,N-dimethyl-p-toluidine). A stabilizer, such as hydroquinone, can alsobe added to the liquid component to prevent premature polymerization ofthe liquid monomer. When the liquid component is mixed with the drycomponent, the dry component begins to dissolve or swell in the liquidmonomer. The amine accelerator reacts with the initiator to form freeradicals that begin to link monomer units to form polymer chains. In thenext two to four minutes, the polymerization process proceeds changingthe viscosity of the mixture from a syrup-like consistency (lowviscosity) into a dough-like consistency (high viscosity). Ultimately,further polymerization and curing occur, causing the cement to hardenand affix a prosthesis to a bone.

In certain aspects of the invention, bone cement 955 or another liquidattachment material such as injectable calciumhydroxyapatite can beinjected into the marrow cavity through one or more openings 950 in theprosthesis. These openings in the prosthesis can extend from thearticular surface to the undersurface of the prosthesis 960. Afterinjection, the openings can be closed with a polymer, silicon, metal,metal alloy or bioresorbable plug.

In another embodiment, one or more components of the articular surfacerepair (e.g., the surface of the system that is pointing towards theunderlying bone or bone marrow) can be porous or porous coated. Avariety of different porous metal coatings have been proposed forenhancing fixation of a metallic prosthesis by bone tissue ingrowth.Thus, for example, U.S. Pat. No. 3,855,638 discloses a surgicalprosthetic device, which may be used as a bone prosthesis, comprising acomposite structure consisting of a solid metallic material substrateand a porous coating of the same solid metallic material adhered to andextending over at least a portion of the surface of the substrate. Theporous coating consists of a plurality of small discrete particles ofmetallic material bonded together at their points of contact with eachother to define a plurality of connected interstitial pores in thecoating. The size and spacing of the particles, which can be distributedin a plurality of monolayers, can be such that the average interstitialpore size is not more than about 200 microns. Additionally, the poresize distribution can be substantially uniform from thesubstrate-coating interface to the surface of the coating. In anotherembodiment, the articular surface repair system can contain one or morepolymeric materials that can be loaded with and release therapeuticagents including drugs or other pharmacological treatments that can beused for drug delivery. The polymeric materials can, for example, beplaced inside areas of porous coating. The polymeric materials can beused to release therapeutic drugs, e.g. bone or cartilage growthstimulating drugs. This embodiment can be combined with otherembodiments, wherein portions of the articular surface repair system canbe bioresorbable. For example, the superficial layer of an articularsurface repair system or portions of its superficial layer can bebioresorbable. As the superficial layer gets increasingly resorbed,local release of a cartilage growth-stimulating drug can facilitateingrowth of cartilage cells and matrix formation.

In any of the methods or compositions described herein, the articularsurface repair system can be pre-manufactured with a range of sizes,curvatures and thicknesses. Alternatively, the articular surface repairsystem can be custom-made for an individual patient.

2.8 Sizing

The articular repair system may be formed or selected so that it willachieve a near anatomic fit or match with the surrounding or adjacentcartilage or subchondral bone or menisci and other tissue. The shape ofthe repair system can be based on the analysis of an electronic image(e.g. MRI, CT, digital tomosynthesis, optical coherence tomography orthe like). If the articular repair system is intended to replace an areaof diseased cartilage or lost cartilage, the near anatomic fit can beachieved using a method that provides a virtual reconstruction of theshape of healthy cartilage in an electronic image.

In one embodiment of the invention, a near normal cartilage surface atthe position of the cartilage defect may be reconstructed byinterpolating the healthy cartilage surface across the cartilage defector area of diseased cartilage. This can, for example, be achieved bydescribing the healthy cartilage by means of a parametric surface (e.g.a B-spline surface), for which the control points are placed such thatthe parametric surface follows the contour of the healthy cartilage andbridges the cartilage defect or area of diseased cartilage. Thecontinuity properties of the parametric surface will provide a smoothintegration of the part that bridges the cartilage defect or area ofdiseased cartilage with the contour of the surrounding healthycartilage. The part of the parametric surface over the area of thecartilage defect or area of diseased cartilage can be used to determinethe shape or part or the shape of the articular repair system to matchwith the surrounding cartilage.

In another embodiment, a near normal cartilage surface at the positionof the cartilage defect or area of diseased cartilage may bereconstructed using morphological image processing. In a first step, thecartilage can be extracted from the electronic image using manual,semi-automated and/or automated segmentation techniques (e.g., manualtracing, region growing, live wire, model-based segmentation), resultingin a binary image. Defects in the cartilage appear as indentations thatmay be filled with a morphological closing operation performed in 2-D or3-D with an appropriately selected structuring element. The closingoperation is typically defined as a dilation followed by an erosion. Adilation operator sets the current pixel in the output image to 1 if atleast one pixel of the structuring element lies inside a region in thesource image. An erosion operator sets the current pixel in the outputimage to 1 if the whole structuring element lies inside a region in thesource image. The filling of the cartilage defect or area of diseasedcartilage creates a new surface over the area of the cartilage defect orarea of diseased cartilage that can be used to determine the shape orpart of the shape of the articular repair system to match with thesurrounding cartilage or subchondral bone.

As described above, the articular repair system may be formed orselected from a library or database of systems of various sizes,curvatures and thicknesses so that it will achieve a near anatomic fitor match with the surrounding or adjacent cartilage and/or subchondralbone. These systems can be pre-made or made to order for an individualpatient. In order to control the fit or match of the articular repairsystem with the surrounding or adjacent cartilage or subchondral bone ormenisci and other tissues preoperatively, a software program may be usedthat projects the articular repair system over the anatomic positionwhere it will be implanted. Suitable software may be commerciallyavailable and/or readily modified or designed by a skilled programmer.

In yet another embodiment, the articular surface repair system may beprojected over the implantation site using one or more 3-D images. Thecartilage and/or subchondral bone and other anatomic structures areextracted from a 3-D electronic image such as an MRI or a CT usingmanual, semi-automated and/or automated segmentation techniques. A 3-Drepresentation of the cartilage and/or subchondral bone and otheranatomic structures as well as the articular repair system is generated,for example using a polygon or NURBS surface or other parametric surfacerepresentation. For a description of various parametric surfacerepresentations see, for example Foley, J. D. et al., Computer Graphics:Principles and Practice in C; Addison-Wesley, 2.sup.nd edition, 1995).The 3-D representations of the cartilage and/or subchondral bone andother anatomic structures and the articular repair system can be mergedinto a common coordinate system. The articular repair system can then beplaced at the desired implantation site. The representations of thecartilage, subchondral bone, menisci and other anatomic structures andthe articular repair system are rendered into a 3-D image, for exampleapplication programming interfaces (APIs) OpenGL® (standard library ofadvanced 3-D graphics functions developed by SGI, Inc.; available aspart of the drivers for PC-based video cards, for example fromwww.nvidia.com for NVIDIA video cards or www.3dlabs.com for 3Dlabsproducts, or as part of the system software for Unix workstations) orDirectX® (multimedia API for Microsoft Windows® based PC systems;available from www.microsoft.com). The 3-D image may be rendered showingthe cartilage, subchondral bone, menisci or other anatomic objects, andthe articular repair system from varying angles, e.g. by rotating ormoving them interactively or non-interactively, in real-time ornon-real-time. The software can be designed so that the articular repairsystem with the best fit relative to the cartilage and/or subchondralbone is automatically selected, for example using some of the techniquesdescribed above. Alternatively, the operator can select an articularrepair system and project it or drag it onto the implantation site usingsuitable tools and techniques. The operator can move and rotate thearticular repair systems in three dimensions relative to theimplantation site and can perform a visual inspection of the fit betweenthe articular repair system and the implantation site. The visualinspection can be computer assisted. The procedure can be repeated untila satisfactory fit has been achieved. The procedure can be entirelymanual by the operator; it can, however, also be computer-assisted. Forexample, the software may select a first trial implant that the operatorcan test. The operator can evaluate the fit. The software can bedesigned and used to highlight areas of poor alignment between theimplant and the surrounding cartilage or subchondral bone or menisci orother tissues. Based on this information, the software or the operatorcan select another implant and test its alignment. One of skill in theart will readily be able to select, modify and/or create suitablecomputer programs for the purposes described herein.

In another embodiment, the implantation site may be visualized using oneor more cross-sectional 2-D images. Typically, a series of 2-Dcross-sectional images will be used. The 2-D images can be generatedwith imaging tests such as CT, MRI, digital tomosynthesis, ultrasound,or optical coherence tomography using methods and tools known to thoseof skill in the art. The articular repair system can then besuperimposed onto one or more of these 2-D images. The 2-Dcross-sectional images can be reconstructed in other planes, e.g. fromsagittal to coronal, etc. Isotropic data sets (e.g., data sets where theslice thickness is the same or nearly the same as the in-planeresolution) or near isotropic data sets can also be used. Multipleplanes can be displayed simultaneously, for example using a split screendisplay. The operator can also scroll through the 2-D images in anydesired orientation in real time or near real time; the operator canrotate the imaged tissue volume while doing this. The articular repairsystem can be displayed in cross-section utilizing different displayplanes, e.g. sagittal, coronal or axial, typically matching those of the2-D images demonstrating the cartilage, subchondral bone, menisci orother tissue. Alternatively, a three-dimensional display can be used forthe articular repair system. The 2-D electronic image and the 2-D or 3-Drepresentation of the articular repair system can be merged into acommon coordinate system. The cartilage repair system can then be placedat the desired implantation site. The series of 2-D cross-sections ofthe anatomic structures, the implantation site and the articular repairsystem may be displayed interactively (e.g. the operator can scrollthrough a series of slices) or non-interactively (e.g. as an animationthat moves through the series of slices), in real-time or non-real-time.

The software can be designed so that the articular repair system withthe best fit relative to the cartilage and/or subchondral bone isautomatically selected, for example using one or more of the techniquesdescribed above. Alternatively, the operator can select an articularrepair system and project it or drag it onto the implantation sitedisplayed on the cross-sectional 2-D images. The operator can move androtate the articular repair system relative to the implantation site andscroll through a cross-sectional 2-D display of the articular repairsystem and of the anatomic structures. The operator can perform a visualand/or computer-assisted inspection of the fit between the articularrepair system and the implantation site. The procedure can be repeateduntil a satisfactory fit has been achieved. The procedure can beentirely manual by the operator; it can, however, also becomputer-assisted. For example, the software may select a first trialimplant that the operator can test (e.g., evaluate the fit). Softwarethat highlights areas of poor alignment between the implant and thesurrounding cartilage or subchondral bone or menisci or other tissuescan also be designed and used. Based on this information, the softwareor the operator can select another implant and test its alignment.

3.0 Implantation

Following one or more manipulations (e.g., shaping, growth, development,etc), the cartilage replacement or regenerating material can then beimplanted into the area of the defect. Implantation can be performedwith the cartilage replacement or regenerating material still attachedto the base material or removed from the base material. Any suitablemethods and devices may be used for implantation, for example, devicesas described in U.S. Pat. Nos. 6,375,658; 6,358,253; 6,328,765; andInternational Publication WO 01/19254.

In selected cartilage defects, the implantation site can be preparedwith a single cut across the articular surface (FIG. 10). In this case,single 1010 and multi-component 1020 prostheses can be utilized.

3.1 Surgical Tools

Further, surgical assistance can be provided by using a device appliedto the outer surface of the articular cartilage or the bone in order tomatch the alignment of the articular repair system and the recipientsite or the joint. The device can be round, circular, oval, ellipsoid,curved or irregular in shape. The shape can be selected or adjusted tomatch or enclose an area of diseased cartilage or an area slightlylarger than the area of diseased cartilage. Alternatively, the devicecan be designed to be substantially larger than the area of diseasedcartilage. Such devices are typically preferred when replacement of amajority or an entire articular surface is contemplated.

Mechanical devices can be used for surgical assistance (e.g., surgicaltools), for example using gels, molds, plastics or metal. One or moreelectronic images can be obtained providing object coordinates thatdefine the articular and/or bone surface and shape. These objectscoordinates can be utilized to either shape the device, e.g. using aCAD/CAM technique, to be adapted to a patient's articular anatomy or,alternatively, to select a typically pre-made device that has a good fitwith a patient's articular anatomy. The device can have a surface andshape that will match all or portions of the articular or bone surfaceand shape, e.g. similar to a “mirror image.” The device can includeapertures, slots and/or holes to accommodate surgical instruments suchas drills and saws. Typically, a position will be chosen that willresult in an anatomically desirable cut plane or drill hole orientationfor subsequent placement of an articular repair system. Moreover, thedevice can be designed so that the depth of the drill can be controlled,e.g., the drill cannot go any deeper into the tissue than defined by thethickness of the device, and the size of the hole in block can bedesigned to essentially match the size of the implant. Information aboutother joints or axis and alignment information of a joint or extremitycan be included when selecting the position of these slots or holes.

In certain embodiments, the surgical assistance device comprises anarray of adjustable, closely spaced pins (e.g., plurality ofindividually moveable mechanical elements). One or more electronicimages can be obtained providing object coordinates that define thearticular and/or bone surface and shape. These objects coordinates canbe entered or transferred into the device, for example manually orelectronically, and the information can be used to create a surface andshape that will match all or portions of the articular and/or bonesurface and shape by moving one or more of the elements, e.g. similar toa “mirror image.” The device can include slots and holes to accommodatesurgical instruments such as drills and saws. The position of theseslots and holes can be adjusted by moving one or more of the mechanicalelements. Typically, a position will be chosen that will result in ananatomically desirable cut plane or drill hole orientation forsubsequent placement of an articular repair system. Information aboutother joints or axis and alignment information of a joint or extremitycan be included when selecting the position of these slots or holes.

In another embodiment, a frame can be applied to the bone or thecartilage in areas other than the diseased bone or cartilage. The framecan include holders and guides for surgical instruments. The frame canbe attached to one or preferably more previously defined anatomicreference points. Alternatively, the position of the frame can becross-registered relative to one, preferably more anatomic landmarks,using an imaging test, for example one or more fluoroscopic imagesacquired intraoperatively. One or more electronic images can be obtainedproviding object coordinates that define the articular and/or bonesurface and shape. These objects coordinates can be entered ortransferred into the device, for example manually or electronically, andthe information can be used to move one or more of the holders or guidesfor surgical instruments. Typically, a position will be chosen that willresult in a surgically or anatomically desirable cut plane or drill holeorientation for subsequent placement of an articular repair system.Information about other joints or axis and alignment information of ajoint or extremity can be included when selecting the position of theseslots or holes.

For example, when a total knee arthroplasty is contemplated, the patientcan undergo an imaging test that will demonstrate the articular anatomyof a knee joint, e.g. width of the femoral condyles, the tibial plateauetc. Additionally, other joints can be included in the imaging testthereby yielding information on femoral and tibial axes, deformitiessuch as varus and valgus and other articular alignment. The imaging testcan be an x-ray image, preferably in standing, load-bearing position, aCT scan or an MRI scan or combinations thereof. The articular surfaceand shape as well as alignment information generated with the imagingtest can be used to shape the surgical assistance device or can beentered into the surgical assistance device and can be used to definethe preferred location and orientation of saw guides or drill holes orguides for reaming devices. Intraoperatively, the surgical assistancedevice is applied to the femoral condyle(s) and subsequently the tibialplateau(s) by matching its surface with the articular surface or byattaching it to anatomic reference points on the bone or cartilage. Thesurgeon can then introduce a saw through the saw guides and prepare thejoint for the implantation. By cutting the cartilage and bone alonganatomically defined planes, a more reproducible placement of theimplant can be achieved. This can ultimately result in improvedpostoperative results by optimizing biomechanical stresses applied tothe implant and surrounding bone for the patient's anatomy.

Thus, surgical tools described herein may also be designed and used tocontrol drill alignment, depth and width, for example when preparing asite to receive an implant. (See, FIGS. 13, 15 and 16). For example, thetools described herein, which typically conform to the joint surface,may provide for improved drill alignment and more accurate placement ofany implant. An anatomically correct tool can be constructed by a numberof methods and may be made of any material, preferably a translucentmaterial such as plastic, lucite, silastic, SLA or the like, andtypically is a block-like shape prior to molding.

Furthermore, re-useable tools (e.g., molds) may be also be created andemployed. Non-limiting examples of re-useable materials include puttiesand other deformable materials (e.g., an array of adjustable closelyspaced pins that can be configured to match the topography of a jointsurface). In these embodiments, the mold may be created directly fromthe joint during surgery or, alternatively, created from an image of thejoint, for example, using one or more computer programs to determineobject coordinates defining the surface contour of the joint andtransferring (e.g., dialing-in) these coordinates to the tool.Subsequently, the tool can be aligned accurately over the joint and,accordingly, the drill and implant will be more accurately placed in andover the articular surface.

In both single-use and re-useable embodiments, the tool can be designedso that the depth of the block controls the depth of the drill, i.e.,the drill cannot go any deeper into the tissue than the depth of block,and the size of the hole in block can be designed to essentially matchthe size of the implant. The tool can be used for general prosthesisimplantation, including, but not limited to, the articular repairimplants described herein and for reaming the marrow in the case of atotal arthroplasty.

These surgical tools (devices) can also be used to remove an area ofdiseased cartilage and underlying bone or an area slightly larger thanthe diseased cartilage and underlying bone. In addition, the device canbe used on a “donor,” e.g., a cadaveric specimen to obtain implantablerepair material. The device is typically positioned in the same generalanatomic area in which the tissue was removed in the recipient. Theshape of the device is then used to identify a donor site providing aseamless or near seamless match between the donor tissue sample and therecipient site. This is achieved by identifying the position of thedevice in which the articular surface in the donor, e.g. a cadavericspecimen has a seamless or near seamless contact with the inner surfacewhen applied to the cartilage.

The device can be molded, machined or formed based on the size of thearea of diseased cartilage and based on the curvature of the cartilageor the underlying subchondral bone or a combination of both. The devicecan then be applied to the donor, (e.g., a cadaveric specimen) and thedonor tissue can be obtained with use of a blade or saw or other tissuecutting device. The device can then be applied to the recipient in thearea of the diseased cartilage and the diseased cartilage and underlyingbone can be removed with use of a blade or saw or other tissue cuttingdevice whereby the size and shape of the removed tissue containing thediseased cartilage will closely resemble the size and shape of the donortissue. The donor tissue can then be attached to the recipient site. Forexample, said attachment can be achieved with use of screws or pins(e.g., metallic, non-metallic or bioresorable) or other fixation meansincluding but not limited to a tissue adhesive. Attachment can bethrough the cartilage surface or alternatively, through the marrowspace.

The implant site can be prepared with use of a robotic device. Therobotic device can use information from an electronic image forpreparing the recipient site.

Identification and preparation of the implant site and insertion of theimplant can be supported by an image-guided surgery system (surgicalnavigation system). In such a system, the position or orientation of asurgical instrument with respect to the patient's anatomy is tracked inreal-time in one or more 2D or 3D images. These 2D or 3D images canimages or can be calculated from images that were acquiredpreoperatively, such as MR or CT images. The position and orientation ofthe surgical instrument is determined from markers attached to theinstrument. These markers can be located by a detector using, forexample, optical, acoustical or electromagnetic signals.

Identification and preparation of the implant site and insertion of theimplant can also be supported with use of a C-arm system. The C-armsystem can afford imaging of the joint in one or, more preferred,multiple planes. The multiplanar imaging capability can aid in definingthe shape of an articular surface. This information can be used toselected an implant with a good fit to the articular surface. Currentlyavailable C-arm systems also afford cross-sectional imaging capability,for example for identification and preparation of the implant site andinsertion of the implant. C-arm imaging can be combined withadministration of radiographic contrast.

In still other embodiments, the surgical devices described herein caninclude one or more materials that harden to form a mold of thearticular surface. A wide-variety of materials that harden in situ havebeen described including polymers that can be triggered to undergo aphase change, for example polymers that are liquid or semi-liquid andharden to solids or gels upon exposure to air, application ofultraviolet light, visible light, exposure to blood, water or otherionic changes. (See, also, U.S. Pat. No. 6,443,988 and documents citedtherein). Non-limiting examples of suitable curable and hardeningmaterials include polyurethane materials (e.g., U.S. Pat. Nos.6,443,988, 5,288,797, 4,098,626 and 4,594,380; and Lu et al. (2000)BioMaterials 21(15):1595-1605 describing porous poly(L-lactide acidfoams); hydrophilic polymers as disclosed, for example, in U.S. Pat. No.5,162,430; hydrogel materials such as those described in Wake et al.(1995) Cell Transplantation 4(3):275-279, Wiese et al. (2001) J.Biomedical Materials Research 54(2):179-188 and Marler et al. (2000)Plastic Reconstruct. Surgery 105(6):2049-2058; hyaluronic acid materials(e.g., Duranti et al. (1998) Dermatologic Surgery 24(12):1317-1325);expanding beads such as chitin beads (e.g., Yusof et al. (2001) J.Biomedical Materials Research 54(1):59-68); and/or materials used indental applications (See, e.g., Brauer and Antonucci, “DentalApplications” pp. 257-258 in “Concise Encyclopedia of Polymer Scienceand Engineering” and U.S. Pat. No. 4,368,040). Any biocompatiblematerial that is sufficiently flowable to permit it to be delivered tothe joint and there undergo complete cure in situ under physiologicallyacceptable conditions can be used. The material may also bebiodegradable.

The curable materials can be used in conjunction with a surgical tool asdescribed herein. For example, the surgical tool may include one or moreapertures therein adapted to receive injections and the curablematerials can be injected through the apertures. Prior to solidifying insitu the materials will conform to the articular surface facing thesurgical tool and, accordingly, will form a mirror image impression ofthe surface upon hardening thereby recreating a normal or near normalarticular surface. In addition, curable materials or surgical tools canalso be used in conjunction with any of the imaging tests and analysisdescribed herein, for example by molding these materials or surgicaltools based on an image of a joint.

4.0 Kits

Also described herein are kits comprising one or more of the methods,systems and/or compositions described herein. In particular, a kit mayinclude one or more of the following: instructions (methods) ofobtaining electronic images; systems or instructions for evaluatingelectronic images; one or more computer means capable of analyzing orprocessing the electronic images; and/or one or more surgical tools forimplanting an articular repair system. The kits may include othermaterials, for example, instructions, reagents, containers and/orimaging aids (e.g., films, holders, digitizers, etc.).

The following examples are included to more fully illustrate the presentinvention. Additionally, these examples provide preferred embodiments ofthe invention and are not meant to limit the scope thereof.

Example 1 Design and Construction of a Three-Dimensional ArticularRepair System

Areas of cartilage are imaged as described herein to detect areas ofcartilage loss and/or diseased cartilage. The margins and shape of thecartilage and subchondral bone adjacent to the diseased areas aredetermined. The thickness of the cartilage is determined. The size ofthe articular repair system is determined based on the abovemeasurements. (FIGS. 12-14). In particular, the repair system is eitherselected (based on best fit) from a catalogue of existing, pre-madeimplants with a range of different sizes and curvatures orcustom-designed using CAD/CAM technology. The library of existing shapesis typically on the order of about 30 sizes.

The implant is a chromium cobalt implant (see also FIGS. 12-14 and17-19). The articular surface is polished and the external dimensionsslightly greater than the area of diseased cartilage. The shape isadapted to achieve perfect or near perfect joint congruity utilizingshape information of surrounding cartilage and underlying subchondralbone. Other design features of the implant may include: a slanted (60-to 70-degree angle) interface to adjacent cartilage; a broad-based basecomponent for depth control; a press fit design of base component; aporous coating of base component for ingrowth of bone and rigidstabilization; a dual peg design for large defects implantstabilization, also porous coated (FIG. 12A); a single stabilizer strutwith tapered, four fin and step design for small, focal defects, alsoporous coated (FIG. 12B); and a design applicable to femoral resurfacing(convex external surface) and tibial resurfacing (concave externalsurface).

Example 2 Minimally Invasive, Arthroscopically Assisted SurgicalTechnique

A. Broad-Based Cartilage Defect

The articular repair systems are inserted using arthroscopic assistance.The device does not require the 15 to 30 cm incision utilized inunicompartmental and total knee arthroplasties. The procedure isperformed under regional anesthesia, typically epidural anesthesia. Thesurgeon may apply a tourniquet on the upper thigh of the patient torestrict the blood flow to the knee during the procedure. The leg isprepped and draped in sterile technique. A stylette is used to createtwo small 2 mm ports at the anteromedial and the anterolateral aspect ofthe joint using classical arthroscopic technique. The arthroscope isinserted via the lateral port. The arthroscopic instruments are insertedvia the medial port. The cartilage defect is visualized using thearthroscope. A cartilage defect locator device is placed inside thediseased cartilage. The probe has a U-shape, with the first arm touchingthe center of the area of diseased cartilage inside the joint and thesecond arm of the U remaining outside the joint. The second arm of the Uindicates the position of the cartilage relative to the skin. Thesurgeon marks the position of the cartilage defect on the skin. A 3 cmincision is created over the defect. Tissue retractors are inserted andthe defect is visualized.

A translucent Lucite block matching the 3D shape of the adjacentcartilage and the cartilage defect is placed over the cartilage defect(FIG. 13). For larger defects, the Lucite block includes a lateral slotfor insertion of a saw. The saw is inserted and a straight cut is madeacross the articular surface, removing an area slightly larger than thediseased cartilage. The center of the Lucite block contains two drillholes with a 7.2 mm diameter. A 7.1 mm drill with drill guidecontrolling the depth of tissue penetration is inserted via the drillhole. Holes for the cylindrical pegs of the implant are created. Thedrill and the Lucite block are subsequently removed.

A plastic model/trial implant of the mini-repair system matching theouter dimensions of the implant is then inserted. The trial implant isutilized to confirm anatomic placement of the actual implant. Ifindicated, the surgeon can make smaller adjustments at this point toimprove the match, e.g. slight expansion of the drill holes oradjustment of the cut plane.

The implant is then inserted with the pegs pointing into the drillholes. Anterior and posterior positions of the implant are color-coded;specifically the anterior peg is marked with a red color and a smallletter “A”, while the posterior peg has a green color and a small letter“P”. Similarly, the medial aspect of the implant is color-coded yellowand marked with a small letter “M” and the lateral aspect of the implantis marked with a small letter “L”. The Lucite block is then placed onthe external surface of the implant and a plastic hammer is used togently advance the pegs into the drill holes. The pegs are designed toachieve a press fit.

The same technique can be applied in the tibia. The implant has aconcave articular surface matching the 3D shape of the tibial plateau.Immediate stabilization of the device can be achieved by combining itwith bone cement if desired.

B. Small, Focal Cartilage Defect

After identification of the cartilage defect and marking of the skinsurface using the proprietary U-shaped cartilage defect locator deviceas described herein, a 3 cm incision is placed and the tissue retractorsare inserted. The cartilage defect is visualized.

A first Lucite block matching the 3D surface of the femoral condyle isplaced over the cartilage defect. The central portion of the Luciteblock contains a drill hole with an inner diameter of, for example, 1.5cm, corresponding to the diameter of the base plate of the implant. Astandard surgical drill with a drill guide for depth control is insertedthrough the Lucite block, and the recipient site is prepared for thebase component of the implant. The drill and the Lucite block are thenremoved.

A second Lucite block of identical outer dimensions is then placed overthe implant recipient site. The second Lucite block has a rounded,cylindrical extension matching the size of the first drill hole (andmatching the shape of the base component of the implant), with adiameter 0.1 mm smaller than the first drill hole and 0.2 mm smallerthan that of the base of the implant. The cylindrical extension isplaced inside the first drill hole.

The second Lucite block contains a drill hole extending from theexternal surface of the block to the cylindrical extension. The innerdiameter of the second drill hole matches the diameter of the distalportion of the fin-shaped stabilizer strut of the implant, e.g. 3 mm. Adrill, e.g. with 3 mm diameter, with a drill guide for depth control isinserted into the second hole and the recipient site is prepared for thestabilizer strut with four fin and step design. The drill and the Luciteblock are then removed.

A plastic model/trial implant matching the 3-D shape of the finalimplant with a diameter of the base component of 0.2 mm less than thatof the final implant and a cylindrical rather than tapered strutstabilizer with a diameter of 0.1 mm less than the distal portion of thefinal implant is then placed inside the cartilage defect. The plasticmodel/trial implant is used to confirm alignment of the implant surfacewith the surrounding cartilage. The surgeon then performs finaladjustments.

The implant is subsequently placed inside the recipient site. Theanterior fin of the implant is marked with red color and labeled “A.”The posterior fin is marked green with a label “P” and the medial fin iscolor coded yellow with a label “M.” The Lucite block is then placedover the implant. A plastic hammer is utilized to advance the implantslowly into the recipient site. A press fit is achieved with help of thetapered and four fin design of the strut, as well as the slightlygreater diameter (0.1 mm) of the base component relative to the drillhole. The Lucite block is removed. The tissue retractors are thenremoved. Standard surgical technique is used to close the 3 cm incision.The same procedure described above for the medial femoral condyle canalso be applied to the lateral femoral condyle, the medial tibialplateau, the lateral tibial plateau and the patella. Immediatestabilization of the device can be achieved by combining it with bonecement if desired.

What is claimed is:
 1. A kit for surgically repairing a joint of a patient comprising: a single use surgical tool having a surface that substantially conforms to a portion of an articular surface of the joint of the patient, wherein the surface of the single use surgical tool has a shape derived from electronic image data of the joint of the patient; and an articular repair system custom made for the patient, wherein the articular repair system includes an implant, wherein the single use surgical tool includes one or more guides that facilitate placement of the implant at a predetermined position or orientation. 